Major
Atorvastatin × Ketoconazole
HMG-CoA reductase inhibitors (statins)×Systemic antimycotics. Imidazole derivatives
Mechanism
Ketoconazole strongly inhibits CYP3A4 – the main atorvastatin metabolic route. Atorvastatin plasma levels rise 3- to 4-fold. FDA Lipitor 2017 advises avoiding concomitant use.
Symptoms
Pain and weakness in large muscle groups (thighs, shoulders, calves), dark urine, elevated creatine kinase. Severe cases progress to rhabdomyolysis with acute kidney injury. Symptoms appear within 1–4 weeks of co-administration.
Management
During ketoconazole therapy, hold atorvastatin or switch to pravastatin/rosuvastatin (no CYP3A4 dependence). Alternative antifungals: terbinafine for dermatophytosis or echinocandins for systemic mycoses.